177 Genetic Predictors of Local Failure Following Conventional Radiation Therapy for Spine Metastases. Issue Volume 65:Issue CN(2018)Supplement 1 (16th August 2018)

• Record Type: Journal Article
• Authors: Lockney, Dennis T; Anderson, Erik S; Lockney, Natalie; Samstein, Robert; Higginson, Daniel; Yamada, Yoshiya Josh; Bilsky, Mark H; Laufer, Ilya; Schmitt, Adam
• Is Part Of: Neurosurgery. Volume 65:Issue CN(2018)Supplement 1
• Page Start: 107
• Page End: 107
• Publication Date: 2018-08-16
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyy303.177
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: INTRODUCTION: Progression of osseous metastases following conventional radiation therapy (RT) to the spine is common. Identification of molecular alterations associated with increased risk of local failure following spine RT may allow stratification of which patients should receive upfront spine stereotactic body radiotherapy (SBRT) rather than conventional RT. METHODS: A retrospective review was performed of an institutional database of 125 patients with lung (n = 35), prostate (n = 27), and breast cancer (n = 63) who underwent conventional spine RT from 2012 to 2016. Patients who underwent targeted tumor mutational sequencing of 468 genes with the MSK-IMPACT platform were included. Patient demographics, treatment characteristics, local control, and survival outcomes were collected. Local failure was defined by imaging and pathology, when available. Risk of local progression was examined for each gene mutated at a frequency of >5% in a model with death treated as a competing risk, and compared with Gray's test for significance. RESULTS: MSK-IMPACT analysis revealed 16 genes mutated at a rate >5% that were tested for association with local failure. The median number of mutations per patient was 4 (range: 0-41). Local failure occurred in 41% of patients, while death occurred in 66% of patients. With death treated as a competing risk, local failure was more common in patients with KEAP1 mutation (HR 2.91, 95% confidence interval [CI] 1.49-5.59, P = .0018) and NF1 mutations (HR = 1.98, 95% CI 1.11-3.54, P = .02). Mutations in other frequently mutated genes were not associated with risk of local failure, including TP53 ( P = .11), PIK3CA ( P = .53), and EGFR ( P = .56). CONCLUSION: Local failure is common after conventional RT for spine metastases. Patients with lung, prostate, and breast tumors who harbor somatic KEAP1 and NF1 mutations are at increased risk of treatment failure. Further validation of these results in a large cohort may allow for identification of patients who may benefit from upfront SBRT.